A randomized trial to compare the efficacy and tolerability of sodium picosulfate-magnesium citrate solution vs. 4 L polyethylene glycol solution as a bowel preparation for colonoscopy.

PURPOSE: The purpose of this study is to compare the efficacy and acceptability of an evening-before regimens of sodium picosulfate/magnesium citrate (SPMC) and polyethylene glycol (PEG) as bowel cleansers and to explore the results of a same-day regimen of SPMC. METHODS: Multicenter, randomized, observer-blinded, parallel study carried out in subjects who were 18-80 years old and were undergoing diagnostic colonoscopy for the first time. The primary outcome was treatment success, which was a composite outcome defined by (1) the evaluation of the overall preparation quality as "excellent" or "good" by two blinded independent evaluators with the Fleet(®) Grading Scale for Bowel Cleansing and (2) a subject's acceptability rating of "easy to take" or "tolerable." The primary outcome was analyzed using a logistic regression with site, gender, and age group (age ≥65 years and <65 years) as factors. RESULTS: Four hundred ninety subjects were included in the efficacy evaluation. Although treatment success was significantly higher in subjects assigned to the evening-before regimen of SPMC vs. subjects assigned to the evening-before PEG, when evaluating the two individual components for treatment success, there were significant differences in the ease of completion but not in the quality of preparation. The same-day SPMC regimen was superior to both the evening-before regimen of SPMC and PEG in terms of the quality of preparation, especially regarding the proximal colon. CONCLUSIONS: An evening-before regimen of SPMC is superior to an evening-before regimen of PEG in terms of subject's acceptability. The same-day SPMC regimen provides better cleansing levels in the proximal colon.

Incidence, clinical outcomes, and therapeutic approaches of capsule endoscopy-related adverse events in a large study population.

INTRODUCTION: Capsule endoscopy (CE) has become a first-line tool for small bowel (SB) examination. However, adverse events (AEs), such as CE retention or aspiration, may occur. The aims of this study were to evaluate incidence, clinical outcomes and therapeutic approaches of CE-related AEs in the largest series published to date. METHODS: Data from 5428 procedures performed at 12 institutions between August 2001 and January 2012 were retrospectively analyzed. Baseline patient characteristics; procedure; type, localization and symptoms before/after AEs; previous patency tests performed; therapeutic management and patient's outcome were recorded. RESULTS: The overall incidence of CE-related AEs was 1.9%: 2.0% for SB, 0.9% for esophageal and 0.5% for colon CE. The incidence of capsule retention was significantly higher than capsule aspiration (1.87% vs. 0.003%; p < 0.05), in patients suffering from inflammatory bowel disease (IBD) than in obscure GI bleeding (OGIB) (3.3% vs. 1.5%; p < 0.05) and in patients with the combination of nausea/vomiting, abdominal pain and distension. The SB was the most frequent localization of retention (88.2%). The use of patency tests -except for Patency© capsule- before CE was not a good predictor for AEs. Most of the patients with AEs developed no or mild symptoms (97%) and were managed by non-surgical methods (64.4%). CONCLUSIONS: CE-related AEs are uncommon and difficult to predict by imagiological examinations. SB retention, that is usually asymptomatic, is the most frequent AE. In absence of symptoms, non-surgical management of CE-related AEs is recommended.

TECIPOT: Study for the Evaluation of New Technologies and Process Engineering Applied to the Optimization of Hospital Transfers.

There is a need for coordinating and manage the information flow between clinical, nursing, ancillary, cleaning and administrative staff to optimize patient transfers during admission and discharge. TECIPOT project proposes the incorporation of new technologies associated with the optimization of emergency circuits to improve the efficiency in the management of patients in the center, as well as improve the perception of patients and professionals about the processes of transfers of emergency patients, observation and discharge from the Hospital. The project proposes a 24 month study to evaluate the impact on healthcare processes.

Treatment of insulin resistance with metformin in naïve genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin.

UNLABELLED: Insulin resistance affects sustained virological response (SVR) in chronic hepatitis C. To know whether adding metformin to standard antiviral treatment improves SVR, we conducted a prospective, multicentered, randomized, double-blinded, placebo-controlled trial in 19 Spanish hospitals, including 123 consecutive patients with genotype 1 chronic hepatitis C and insulin resistance. Patients were randomized to receive either metformin (arm A; n = 59) or placebo (arm B; n = 64) in addition to peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). The primary end point was SVR, and secondary endpoints were viral clearance at weeks 12, 24, and 48, and changes in the homeostasis model assessment (HOMA) index over the first 24 weeks. There were no differences between arms at baseline. In the intent-to-treat analysis, SVR was observed in 53% versus 42% in arm A and arm B, respectively (P = NS). In the subgroup analyses, SVR was higher in females (n = 54) receiving metformin: arm A, 58% (15/26) versus 29% (8/28) arm B (P = 0.03). In the per protocol analysis (PPA; n = 101), SVR was 67% in arm A and 49% in arm B (P = 0.06). Viral decline during the first 12 weeks was greater in females receiving metformin: -4.88 (1.18) versus -4.0 (1.44) (P = 0.021), whereas no differences were seen in males. The triple therapy was well tolerated, but diarrhea was more often seen in arm A (34% versus 11%; P < 0.05). CONCLUSION: Adding metformin to peginterferon and ribavirin was safe and improved insulin sensitivity. Although the study failed to show a statistically significant difference between arms, it did show an improved SVR in females.

Esophageal capsule endoscopy for screening and surveillance of esophageal varices in patients with portal hypertension.

UNLABELLED: Bleeding from esophageal varices (EV) is a serious consequence of portal hypertension. Current guidelines recommend screening patients with cirrhosis with esophagogastroduodenoscopy (EGD) to detect varices. However, the unpleasantness and need for sedation of EGD may limit adherence to screening programs. Pilot studies have shown good performance of esophageal capsule endoscopy in detecting varices. This multicenter trial was designed to assess the diagnostic performance of capsule endoscopy in comparison with EGD. Patients undergoing EGD for screening or surveillance of EV underwent a capsule study previously. The study was designed as an equivalence study, assuming that a difference of

COX expression and PGE(2) and PGD(2) production in experimental acute and chronic gastric lesions.

Prostaglandin E(2) and D(2) (PGE(2) and PGD(2)) production and cyclooxygenase-2 (COX-2) expression during the resolution of acute and chronic gastric inflammatory lesions in Wistar rats have been investigated. Differences between ibuprofen, nonselective COX inhibitor, and rofecoxib, specific COX-2 inhibitor, on the development of the induced responses were also analysed. In an acute model, by instillation of HCL, the greatest injury was observed early with a rapid and progressive restoration. Maximal up-regulation of COX-2 protein was detected at 6 h and was accompanied by increase of PGE(2) synthesis but not PGD(2). Both drugs stimulated COX-2 expression in accordance to their capacity of inhibiting this enzymatic activity, driving to delay in the healing. In a chronic model, by acetic acid-induced gastric ulcers, COX-2 was expressed at 7 days and was also associated with PGE(2) increase. Ibuprofen and rofecoxib also augmented COX-2 protein and inhibited PGE(2) levels. However, PGD(2) production was augmented when none signal of COX-2 protein could be detected. Together, this study confirms the role played by COX-2 enzyme in the resolution of acute and chronic gastric inflammatory process, PGE(2) being the principal product. The antiinflammatory effect of nonsteroidal antiinflammatory drugs (NSAIDs) could be mediated not only through the inhibition of COX activity but also through the induction of antiinflammatory PGs production-such as PGD(2)-although further studies would be needed to clarify the mechanisms of this activity and the possible implicated processes.

Mucosal damage induced by preferential COX-1 and COX-2 inhibitors: role of prostaglandins and inflammatory response.

Nonsteroidal anti-inflammatory drugs (NSAID) are well known to induce gastric mucosal damage including bleeding, ulceration and perforation in humans and animals too. These effects are related with the inhibition of the enzyme cyclooxygenase, which is the main established mechanism of action for these drugs. Fasted rats were given piroxicam, preferential COX-1 inhibitor (10-20 mg/kg) or meloxicam, preferential COX-2 inhibitor (7.5-15 mg/kg) orally. Six or nine hours (h) later, respectively, the stomach was excised, the severity of the damage assessed and myeloperoxidase (MPO) activity measured, as well as prostaglandin PGE(2) content. Furthermore, in order to assess the effects of these oxicams over previously damaged gastric mucosa, 1 ml of 0.6 N HCl was administered p.o. followed, 1 h after, of the correspondent dose of each NSAID, and the same parameters were determined. Oral administration of both drugs dose-dependently caused acute gastric haemorrhage erosions. Myeloperoxidase activity was significantly increased by piroxicam administration. In addition, PGE(2) content was significantly reduced. The association between the administration of the acid and NSAID caused a worsening of the damage and, while myeloperoxidase activity did not modify by both piroxicam and meloxicam, PGE(2) levels were reduced. These results suggest that the PG derived from both COX-1 and COX-2 pathway plays a beneficial role in the gastroprotection, and thus caution should be exercise in the clinical use of preferential COX-2 inhibitors.

Agile patency system eliminates risk of capsule retention in patients with known intestinal strictures who undergo capsule endoscopy.

BACKGROUND: Capsule endoscopy (CE) of the small bowel has become a standard diagnostic tool, but there have been concerns regarding the risk of capsule retention in certain high-risk groups. The Agile patency system, an ingestible and dissolvable capsule with an external scanner, was developed to allow physicians to perform CE with greater confidence that the capsule will be safely excreted in patients at risk for capsule retention. OBJECTIVE: Our purpose was to assess the ability of the device to help physicians identify which patients with known strictures may safely undergo CE. DESIGN: Patients with known strictures ingested the new patency capsule and underwent periodic scanning until it was excreted. The intestinal tract was considered to be sufficiently patent if the capsule was excreted intact or if the capsule was not detected by the scanner at 30 hours after ingestion. If patency was established, then standard CE was performed. SETTING: International multicenter study. PATIENTS: A total of 106 patients with known strictures. INTERVENTION: Agile patency system. MAIN OUTCOME MEASUREMENTS: Performance and safety of Agile patency system. RESULTS: A total of 106 patients ingested the patency capsule. Fifty-nine (56%) excreted it intact and subsequently underwent CE. There were no cases of capsule retention. Significant findings on CE were found in 24 (41%). There were 3 severe adverse events. CONCLUSIONS: These results suggest that the Agile patency system is a useful tool for physicians to use before CE in patients with strictures to avoid retention. This group of patients may have a high yield of clinically significant findings at CE. This capsule may determine whether patients who have a contraindication to CE may safely undergo CE and obtain useful diagnostic information.

Complications, limitations, and failures of capsule endoscopy: a review of 733 cases.

BACKGROUND: Although a variety of technical and clinical problems of capsule endoscopy have been reported, their incidence and clinical importance are unknown. The objective was to evaluate the incidence and the type of such events. METHODS: This was a retrospective analysis of 733 consecutive examinations at 4 large referral centers. The main outcome measurements were that the problems were classified as "technical," i.e., related to the functioning of the equipment, and "clinical," i.e., related to patient characteristics. For each type of event, the causes and the impact on the ability to reach a diagnosis were examined. RESULTS: A total of 183 problems were recorded in 174 patients (23.7%): one problem occurred in 165 patients, two in 9 patients. In 8.46% of patients, technical limitations or failures, or clinical complications prevented or hampered diagnosis. Technical problems (e.g., gaps in the recordings, short duration of capsule batteries, failure of downloading) occurred in the early phase of capsule use in 8.6% of examinations and prevented or hampered diagnosis in 2.9%. Clinical problems (difficulty/inability to swallow the capsule, incomplete small-bowel examination) occurred in 16.4% of examinations and hampered or prevented diagnosis in 6.4%. Capsule retention that required surgical or endoscopic retrieval occurred in 1.9% of cases. CONCLUSIONS: Technical problems were rare and hampered or prevented the diagnosis in a very small number of cases. The majority of clinical failures were related to an incomplete small-bowel examination.

Preventive effect of zaprinast and 3-isobutyl, 1-methylxanthine (phosphodiesterase inhibitors) on gastric injury induced by nonsteroidal antiinflammatory drugs in rats.

Cyclic GMP plays an important role in maintaining homeostasis in the gastric mucosa. NSAIDs damage the mucosa by mechanisms that may be mediated by alterations in the intragastric concentration of cyclic GMP. To test this hypothesis we studied the effects of the oral administration of acetylsalicylic acid (100, 300, and 500 mg/kg), piroxicam (5, 10, and 20 mg/kg) and sodium diclofenac (10, 25, 50, and 100 mg/kg), and of their interaction with zaprinast (5 mg/kg) and IBMX (10 mg/kg), on intragastric concentrations of cyclic GMP and the gastric erosive index in rats. All determinations were done 3 hr after the NSAID was given. All NSAIDs induced dose-dependent decreases in mucosal concentrations of cyclic GMP, which correlated inversely with the surface area showing mucosal injury. In contrast, cyclic GMP concentrations remained normal, and no intragastric damage was seen in rats given zaprinast (cyclic GMP-specific phosphodiesterase inhibitor) or IBMX (non-specific phosphodiesterase inhibitor) or in combination with NSAIDs. These findings are in line with the hypothesis that cyclic GMP is involved in the biochemical mechanisms of NSAID-induced gastric injury.

Effects of celecoxib on acid-challenged gastric mucosa of rats: comparison with metamizol and piroxicam.

Selective COX-2 inhibitors have been shown to produce fewer gastrointestinal adverse reactions than classical NSAIDs. Nevertheless, these new agents may worsen and delay the healing of experimentally induced gastric ulcers in animals. In this study, we compared the effects of a selective COX-2 inhibitor (celecoxib), a preferential COX-1 inhibitor (piroxicam), and a nonnarcotic analgesic (metamizol) on normal gastric mucosa of rats and, on the other hand, in a setting of preexisting acute gastric lesions induced by 0.6 N hydrochloric acid. Under normal conditions, only piroxicam produced appreciable gastric lesions. However, after acid challenge the three assayed drugs induced significant macroscopic and microscopic damage. Myeloperoxidase activity as an index of neutrophil infiltration was elevated with celecoxib and piroxicam on normal gastric mucosa. On inflamed mucosa, celecoxib augmented enzymatic activity at the lower dose, which was parallelled by an increase in the interleukin 1beta level. Acid instillaton produced a significant rise in PGE2 content at 7 hr. Drug treatment after acid challenge decreased prostaglandin values in all cases, although to a lesser extent than after single drug dose administration. COX-2 mRNA expression was visible 1 hr after acid application, whereas COX-2 protein could only be detected at 7 hr. Piroxicam increased both expression levels. All NSAIDs enhanced transforming growth factor alpha and epidermal growth factor receptor immunoreactivity around the acid-induced lesions. It is concluded that selective COX-2 inhibitors, like conventional NSAIDs, impair the healing of gastric damage, and therefore special attention should be paid in patients with gastric pathologies.